Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Toxic and metabolic encephalopathies: iconographic essay

Generally, toxic-metabolic diseases affecting the central nervous system can hardly be differentiated just on the basis of their clinical presentation. However, some typical neuroradiological features can guide the correct diagnosis. In this context, magnetic resonance imaging is an important tool which, in association with clinical and laboratory data, can establish an early and specific treatment. The present pictorial essay with selected cases from the archives of the authors' institution describes imaging findings which might help in the etiologic diagnosis of toxic-metabolic diseases.

Arterial hypertension and metabolic profile in patients with polycystic ovary syndrome

PURPOSE: To evaluate parameters related with arterial pressure and metabolic profile in women with polycystic ovary syndrome (POS). METHODS: This monocentric study at the University Hospital Endocrinology Section included 60 women aged 18-45 years, 42 being diagnosed with POS and acting as 18 controls. All women were subjected to transvaginal ultrasound and monitored for arterial pressure for 24 h in the ambulatory (MAP). Venous blood samples were taken between 07.00 and 09.00, after 12 h fasting. Basal (BG) and fasting glucose concentrations, total cholesterol and its fractions, triglycerides and insulin (to calculate the homeostatic assay insulin-resistance, HOMA-IR) were measured. Collected data were the mean arterial blood pressure (24-h awake/sleep cycle), arterial pressure nocturnal descensus, glycemia and fasting glucose for HOMA-IR, and lipid profile. The Student's t test was used to compare homogeneous variables; the Mann-Whitney test was used to compare non-homogeneous variables; the Pearson's correlation coefficient was used to search for correlation between the variables. The c² test was used for comparison of the absence of nocturnal descensus. Significance was taken as p<0.05. RESULTS: The mean age of the patients with POS was 27.4±5.5 (18-45 years, n=42) and the body mass index (BMI) was 30.2±6.5 kg/m² (18.3-54.9). In the Control Group, the mean age was 31.4±6.1 (18-45 years) and the BMI was 27.1±6.2 kg/m² (18.3-54.9, n=18). No difference in the metabolic parameters and insulin resistance was observed between the two groups. Comparison between these parameters and MAP showed that the only parameter with a correlation was the BMI, independent of the POS diagnosis. This was not seen in nocturnal descensus, which was uncorrelated with POS and any of the other studied parameters. CONCLUSION: POS women do not show higher arterial blood pressure, glycemia, HDL-col, TG, HOMA-IR and BMI compared to non-POS women. However, POS patients showed correlation between arterial pressure and BMI, suggesting that obesity is a primary factor involved in arterial pressure changes in these patients.

Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Incidence of congenital toxoplasmosis in the city of Belém, state of Pará, northern Brazil, determined by a neonatal screening program: preliminary results

INTRODUCTION: The aim of this study was to determinate the incidence of congenital toxoplasmosis among a group of newborns (NBs) from Belém using neonatal screening. METHODS: Among the 6,000 newborns referred for investigation of genetic and metabolic diseases, 1,000 were selected for screening for congenital toxoplasmosis by determining the amount of IgM in the eluates of blood collected on filter paper. Positive tests were confirmed using paired serology of the NB and his mother. RESULTS: Out of the 1,000 NBs assessed, one had a positive screening result that was confirmed by paired serology. CONCLUSIONS: The incidence of congenital toxoplasmosis in Belém was 10/10,000 live NBs.

Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

AbstractPhage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.

Dried blood spots as a practical and inexpensive source for human immunodeficiency virus and hepatitis C virus surveillance

Passive surveillance of infectious diseases with a high percentage of asymptomatic cases or long incubation periods, such as acquired immunodeficiency syndrome (AIDS), does not reflect the current transmission dynamics. Thus, a multi-strategic surveillance, such as the human immunodeficiency virus (HIV) sentinel surveillance proposed by the World Health Organization (WHO), is necessary. The Brazilian HIV sentinel surveillance was started in May 1992 with this purpose. The objectives of this study were to evaluate the feasibility and costs of HIV and hepatitis C virus (HCV) surveillance using dried blood spots (DBS) collected for neonatal screening of metabolic diseases in the state of Minas Gerais, Brazil. This was accomplished through the comparison of HIV and HCV seroprevalence with previous Brazilian studies. From December 2001 to June 2002, 24,905 newborns were tested for HIV and 4211 for HCV. HIV seroprevalence was 0.25% and the 95% confidence interval (CI) was 0.18, 0.31%; and HCV seroprevalence was 0.71% and the 95% CI was 0.46, 0.97%. These numbers are similar to previous Brazilian studies. Cost in this study was approximately US$ 3.10 per sample, which was roughly one third of the cost of the same exam at the Brazilian HIV sentinel surveillance. We conclude that it is possible and more cost-effective to use DBS for infectious diseases surveillance, albeit it is still necessary to compare these results with the usual sentinel methodology in a concomitant trial.

Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats

Several investigators have demonstrated that diabetes is associated with autonomic and myocardial dysfunction. Exercise training is an efficient non-pharmacological treatment for cardiac and metabolic diseases. The aim of the present study was to investigate the effects of exercise training on hemodynamic and autonomic diabetic dysfunction. After 1 week of diabetes induction (streptozotocin, 50 mg/kg, iv), male Wistar rats (222 ± 5 g, N = 18) were submitted to exercise training for 10 weeks on a treadmill. Arterial pressure signals were obtained and processed with a data acquisition system. Autonomic function and intrinsic heart rate were studied by injecting methylatropine and propranolol. Left ventricular function was assessed in hearts perfused in vitro by the Langendorff technique. Diabetes (D) bradycardia and hypotension (D: 279 ± 9 bpm and 91 ± 4 mmHg vs 315 ± 11 bpm and 111 ± 4 mmHg in controls, C) were attenuated by training (TD: 305 ± 7 bpm and 100 ± 4 mmHg). Vagal tonus was decreased in the diabetic groups and sympathetic tonus was similar in all animals. Intrinsic heart rate was lower in D (284 ± 11 bpm) compared to C and TD (390 ± 8 and 342 ± 14 bpm, respectively). Peak systolic pressure developed at different pressures was similar for all groups, but +dP/dt max was decreased and -dP/dt max was increased in D. In conclusion, exercise training reversed hypotension and bradycardia and improved myocardial function in diabetic rats. These changes represent an adaptive response to the demands of training, supporting a positive role of physical activity in the management of diabetes.

Inhibition of in vitro CO2 production and lipid synthesis by 2-hydroxybutyric acid in rat brain

2-Hydroxybutyric acid appears at high concentrations in situations related to deficient energy metabolism (e.g., birth asphyxia) and also in inherited metabolic diseases affecting the central nervous system during neonatal development, such as "cerebral" lactic acidosis, glutaric aciduria type II, dihydrolipoyl dehydrogenase (E3) deficiency, and propionic acidemia. The present study was carried out to determine the effect of 2-hydroxybutyric acid at various concentrations (1-10 mM) on CO2 production and lipid synthesis from labeled substrates in cerebral cortex of 30-day-old Wistar rats in vitro. CO2 production was significantly inhibited (30-70%) by 2-hydroxybutyric acid in cerebral cortex prisms, in total homogenates and in the mitochondrial fraction. We also demonstrated a significant inhibition of lipid synthesis (20-45%) in cerebral cortex prisms and total homogenates in the presence of 2-hydroxybutyric acid. However, no inhibition of lipid synthesis occurred in homogenates free of nuclei and mitochondria. The results indicate an impairment of mitochondrial energy metabolism caused by 2-hydroxybutyric acid, a fact that may secondarily lead to reduction of lipid synthesis. It is possible that these findings may be associated with the neuropathophysiology of the situations where 2-hydroxybutyric acid is accumulated.

Plasma free and total carnitine measured in children by tandem mass spectrometry

Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 ± 2.4 and 23.5 ± 2.9; one to twelve months: 28.8 ± 10.2 and 35.9 ± 11.4; one to seven years: 30.7 ± 10.3 and 38.1 ± 11.9; seven to 14 years: 33.7 ± 11.6, and 43.1 ± 13.8 µM, respectively). No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.

ERICA: prevalence of metabolic syndrome in Brazilian adolescents

ABSTRACT OBJECTIVE To determine the prevalence of metabolic syndrome and its components in Brazilian adolescents. METHODS We evaluated 37,504 adolescents who were participants in the Study of Cardiovascular Risks in Adolescents (ERICA), a cross-sectional, school-based, national study. The adolescents, aged from 12 to 17 years, lived in cities with populations greater than 100,000 inhabitants. The sample was stratified and clustered into schools and classes. The criteria set out by the International Diabetes Federation were used to define metabolic syndrome. Prevalences of metabolic syndrome were estimated according to sex, age group, school type and nutritional status. RESULTS Of the 37,504 adolescents who were evaluated: 50.2% were female; 54.3% were aged from 15 to 17 years, and 73.3% were from public schools. The prevalence of metabolic syndrome was 2.6% (95%CI 2.3-2.9), slightly higher in males and in those aged from 15 to 17 years in most macro-regions. The prevalence was the highest in residents from the South macro-region, in the younger female adolescents and in the older male adolescents. The prevalence was higher in public schools (2.8% [95%CI 2.4-3.2]), when compared with private schools (1.9% [95%CI 1.4-2.4]) and higher in obese adolescents when compared with nonobese ones. The most common combinations of components, referring to 3/4 of combinations, were: enlarged waist circumference (WC), low HDL-cholesterol (HDL-c) and high blood pressure; followed by enlarged WC, low HDL-c and high triglycerides; and enlarged WC, low HDL-c, high triglycerides and blood pressure. Low HDL was the second most frequent component, but the highest prevalence of metabolic syndrome (26.8%) was observed in the presence of high triglycerides. CONCLUSIONS ERICA is the first Brazilian nation-wide study to present the prevalence of metabolic syndrome and describe the role of its components. Despite the prevalence of Metabolic Syndrome being low, the high prevalences of some components and participation of others in the syndrome composition shows the importance of early diagnosis of this changes, even if not grouped within the metabolic syndrome.

Acute kidney injury in a tropical country: a cohort study of 253 patients in an infectious diseases intensive care unit

Introduction: Acute kidney injury (AKI) is a frequent and potentially fatal complication in infectious diseases. The aim of this study was to investigate the clinical aspects of AKI associated with infectious diseases and the factors associated with mortality. Methods: This retrospective study was conducted in patients with AKI who were admitted to the intensive care unit (ICU) of a tertiary infectious diseases hospital from January 2003 to January 2012. The major underlying diseases and clinical and laboratory findings were evaluated. Results: A total of 253 cases were included. The mean age was 46±16 years, and 72% of the patients were male. The main diseases were human immunodeficiency virus (HIV) infection, HIV/acquired immunodeficiency syndrome (AIDS) (30%), tuberculosis (12%), leptospirosis (11%) and dengue (4%). Dialysis was performed in 70 cases (27.6%). The patients were classified as risk (4.4%), injury (63.6%) or failure (32%). The time between AKI diagnosis and dialysis was 3.6±4.7 days. Oliguria was observed in 112 cases (45.7%). The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were higher in patients with HIV/AIDS (57±20, p-value=0.01) and dengue (68±11, p-value=0.01). Death occurred in 159 cases (62.8%). Mortality was higher in patients with HIV/AIDS (76.6%, p-value=0.02). A multivariate analysis identified the following independent risk factors for death: oliguria, metabolic acidosis, sepsis, hypovolemia, the need for vasoactive drugs, the need for mechanical ventilation and the APACHE II score. Conclusions: AKI is a common complication in infectious diseases, with high mortality. Mortality was higher in patients with HIV/AIDS, most likely due to the severity of immunosuppression and opportunistic diseases.

Hormonal, metabolic and nutritional alterations in smokers: emergency for smoking abstinence

OBJECTIVE: To evaluate the biochemical and nutritional status of smokers in treatment for smoking cessation and its association with anthropometric parameters. METHODS: This is a cross-sectional study with convenience sample. Adult smokers were assessed at the start of treatment in the Interdisciplinary Center for Tobacco Research and Intervention of the University Hospital of the Federal University of Juiz de Fora (CIPIT/HU-UFJF). We evaluated the body mass index (BMI), conicity index (CI); waist circumference (WC), percentage of body fat (%BF), fasting glycemia, cortisol, insulin, total cholesterol (TC), LDL-c, HDL-c, triglycerides (TG) and metabolic syndrome (MS). RESULTS: Most participants (52.2%) had MS and high cardiovascular risk. The fasting glycemia was abnormal in 30.4%. There was a significant positive correlation between BMI and WC (r = 0.90; p = 0.0001), %BF (r = 0.79; p = 0.0001), CI (r = 0.65; p = 0.0001), glycemia (r = 0.42; p = 0.04) and TG (r = 0.47; p = 0.002). The CI presented positive correction with insulin (r = 0.60; p = 0.001), glycemia (r = 0.55; p = 0.007), TG (r = 0.54; p = 0.008) and %BF (r = 0.43; p = 0.004). Patients with longer duration of smoking had a higher risk of developing MS (OR = 9.6, p = 0.016). CONCLUSION: The smokers evaluated had increased risk for developing MS, especially those with longer duration of smoking, requiring urgent smoking cessation.

Risk Factors for Cardiovascular Disease, Metabolic Syndrome and Sleepiness in Truck Drivers

Abstract Background: Truck driver sleepiness is a primary cause of vehicle accidents. Several causes are associated with sleepiness in truck drivers. Obesity and metabolic syndrome (MetS) are associated with sleep disorders and with primary risk factors for cardiovascular diseases (CVD). We analyzed the relationship between these conditions and prevalence of sleepiness in truck drivers. Methods: We analyzed the major risk factors for CVD, anthropometric data and sleep disorders in 2228 male truck drivers from 148 road stops made by the Federal Highway Police from 2006 to 2011. Alcohol consumption, illicit drugs and overtime working hours were also analyzed. Sleepiness was assessed using the Epworth Sleepiness Scale. Results: Mean age was 43.1 ± 10.8 years. From 2006 to 2011, an increase in neck (p = 0.011) and abdominal circumference (p < 0.001), total cholesterol (p < 0.001), triglyceride plasma levels (p = 0.014), and sleepiness was observed (p < 0.001). In addition, a reduction in hypertension (39.6% to 25.9%, p < 0.001), alcohol consumption (32% to 23%, p = 0.033) and overtime hours (52.2% to 42.8%, p < 0.001) was found. Linear regression analysis showed that sleepiness correlated closely with body mass index (β = 0.19, Raj2 = 0.659, p = 0.031), abdominal circumference (β = 0.24, Raj2 = 0.826, p = 0.021), hypertension (β = -0.62, Raj2 = 0.901, p = 0.002), and triglycerides (β = 0.34, Raj2 = 0.936, p = 0.022). Linear multiple regression indicated that hypertension (p = 0.008) and abdominal circumference (p = 0.025) are independent variables for sleepiness. Conclusions: Increased prevalence of sleepiness was associated with major components of the MetS.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome

Abstract Background: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. Objective: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. Results: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (psex < 0.01). Conclusions: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.